Redox-dependent impairment of vascular function in sickle cell disease

Abstract

The vascular pathophysiology of sickle cell disease (SCD) is influenced by many factors including adhesiveness of red and white blood cells to endothelium, increased coagulation and homeostatic perturbation. The vascular endothelium is central to disease pathogenesis because it displays adhesion molecules for blood cells, balances procoagulant and anticoagulant properties of the vessel wall and regulates vascular homeostasis by synthesizing vasoconstricting and vasodilating substances. Occurrence of intermittent vascular occlusion in SCD leads to reperfusion injury associated with granulocyte accumulation and enhanced production of reactive oxygen species. The participation of nitric oxide (NO) in oxidative reactions causes a reduction in NO bioavailability and contributes to vascular dysfunction in SCD. Therapeutic strategies designed to counteract endothelial, inflammatory and oxidative abnormalities may reduce the frequency of hospitalization, blood transfusion, the incidence of pain and the occurrence of acute chest syndrome and pulmonary hypertension in patients with SCD.

Inhibition of myeloperoxidase decreases vascular oxidative stress and increases vasodilatation in sickle cell disease mice

“…Although KYC treatments tended to decrease ALT in SCD mice (hatched gray versus gray bar), the differences between the means did not achieve statistical signifi cance ( P = 0.07). release MPO, which subsequently enters the vessel wall, increases infl ammation, and generates oxidants that impair vasodilatation ( 15,16 ). Interestingly, KYC decreased not only sL-selectin but also 3-ClTyr, a fi ngerprint biomarker of MPOdependent oxidative stress in the vessel wall of the SCD mice.…”

Stabilization of erythrocytes against oxidative and hypotonic stress by tannins isolated from sumac leaves (Rhus typhina L.) and grape seeds (Vitis vinifera L.)

“…The oxidative stress of erythrocytes accompanies many pathological conditions, such as sickle cell and iron deficiency anemias and thalassemia [8,29,30], as well as aging [17,31], hypoxia [9] and obesity [32]. An intensive search has been going on for natural antioxidants to treat diseases induced by RONS.…”

Physical activity limits pulmonary endothelial activation in sickle cell SAD mice

“…In each of these 3 pedigrees, 1 affected family member carried a 52-base deletion in exon 9 of the CALR gene (not shown), which represents the most frequent form of the CALR mutations (type 1). One of these patients was initially diagnosed with ET 7 and later progressed to PMF (MPN family 1), and the two remaining patients had ET (MPN families 2 and 3). All CALR mutations occurred in patients with an MPN diagnosis, whereas a somatic JAK2-V617F mutation was found in 1 healthy family member with platelets in the upper normal range but otherwise normal blood counts (MPN family 5; data not shown).…”